You can now explore the mRNA expression of your favorite TB gene of interest in our recently published human pulmonary M.tb granuloma single-cell dataset at the Broad Single Cell PORTAL!

@broadinstitute.org
@wallacewly.bsky.social

singlecell.broadinstitute.org/single_cell/...

I’m excited to announce that our paper, describing early and opposing roles for neutrophils and CD4 T cells in determining #TB lesion structure, is out at @jem.org ! Huge thanks to my lab, and the Urdahl, @michael-gerner.bsky.social, and Aitchison labs who made this possible

doi.org/10.1084/jem....

Targeting infection-specific peptides in immunopeptidomics studies for vaccine target discovery MS-based immunopeptidomics can facilitate vaccine antigen discovery, but self-MHC peptides greatly outnumber pathogen-derived MHC peptides, presenting a ch

Newest paper from the lab out today (doi.org/10.1084/jem....)! Here, we describe PathMHC, a novel MS-based approach to identify rare pathogen-derived peptides on MHC-I and MHC-II. We apply this to a range of pathogens Mtb, SARS-CoV-2, and Listeria.

A Scientific Brain Drain Has Followed Trump’s Gutting Of The NIH - Dr. Francis Collins YouTube video by The Late Show with Stephen Colbert

youtu.be/lW9c6t4potU?...

I also had never seen this format until our preprint was reviewed. Seems to be mostly preprint-focused. Anyways, thanks for sharing the biorxiv link 😊

Thank you to @amitava-bio.bsky.social and Thomas Weichhart for this really nice summary of our preprint! www.nature.com/articles/s41...

We are looking for post-docs interested in studying T cell responses to M. tuberculosis infection…especially basic T cell immunologists who are interested in learning to work with BSL3 pathogens. The NIH intramural program is an amazing place to train!

It's world TB day.

The last two months have been a series of attacks on global health, infectious disease science and vulnerable populations. The damage will take decades to undo, and we are heading onto a steep global health disaster.

We can't stay quiet.
#tuberculosis #TB #WTBD2025

Today is the 24th of March and it's World TB Day. We typically have many activities to educate and raise awareness about TB and how important it is for us all to commit to doing more to end TB! This year feels different though.

Register | Turmoil, TB Care, & Taking Action Join experts on World TB Day to discuss the history, innovations, and social justice impact of TB, the world’s deadliest infectious disease.

For World TB Day, PIH is hosting a webinar at 12pm EST to discuss the repercussions of recently slashed US foreign aid and the hope that remains. #worldTBday @partnersinhealth.bsky.social

Register here:
act.pih.org/worldtbday2025

I recommend hating tuberculosis. It has fueled me like no other hate that came before.

Thanks, Tom!

Thank you Alissa! Moving, starting up the lab, and getting this submitted felt like an extreme sport 😅 Very grateful to have a supportive community at NIH and the always inspiring early career TB research crew to look up to (like you 😉)

P.S. SO bummed I couldn't be at KS to catch up!

But microbial factors could be at play. Especially since we know Mtb resides in the caseum and prompts macrophage necrosis. We are hoping some of our organoid work will help us decouple the chicken-and-egg relationship between hypoxia and bacterial burden.

This is a great question. To try to get at it, we are currently evaluating granulomas from an earlier timepoint of infection. These grans have much higher CFU but less hypoxia. The main thrust of hypoxia appears to be caseation and it may be exacerbated by the degree of neutrophil influx...

Thank you! We are excited to finally be able to share it with everyone.

Thanks for tuning in! Please feel free to reach out with any feedback or questions on our preprint. (20/20)

The senior authors on this paper (especially my PhD advisor, Mike Angelo) have been the most incredible mentors to me and the wind behind my sails as I transitioned from Stanford to the NIH to start my own group. Despite...everything 🙃...I am excited for the cool science we are cooking up! (19/20)

In Nov 2023 I started my lab at the NIH (the Spatial Immunology Unit) as an Independent Research Scholar. We are combining spatial mapping of tissues with functional assays in organoid models to define the principles of immune programming during infection and inflammation with a focus on TB. (18/20)

A HUGE thank you my co-author, Alea Delmastro, who began as my undergrad mentee in 2018, adapted MIBI for NHP tissues (no small feat), and then became my co-lead on this study. Here we are celebrating after we stained the study cohort during the pandemic (a culmination of 3 years of work). (17/20)

I would like to thank the extremely creative, talented, and hard-working individuals who worked on this study. This team spans 8 institutions and much of this work was done in the depths of the pandemic. I am so grateful for their brilliance, collaboration, and friendship. (16/20)

The immunometabolic topography of tuberculosis granulomas governs cellular organization and bacterial control Despite being heavily infiltrated by immune cells, tuberculosis (TB) granulomas often subvert the host response to Mycobacterium tuberculosis (Mtb) infection and support bacterial persistence. We prev...

Check out the full preprint for more details, our perspective on what this means for clinical management of TB, and parallels between hypoxia in TB granulomas and other settings of inflammation. (15/20) www.biorxiv.org/content/10.1...

Moral of the story? Granuloma hypoxia is associated with pathologic immune cell states, dysfunctional cellular organization of the granuloma, and a near-complete blockade of lymphocyte infiltration that would be required for a successful host response. (14/20)

Lastly, we confirmed that the same phenomenon of immunometabolic zonation is present in human pulmonary TB, underscoring the translational relevance of our findings. (13/20)

We also applied QUICHE (from the talented Jolene Ranek in the Angelo lab) to map the spatial networks of low- versus high-bacterial burden granulomas. With this analysis we found that hypoxia-associated spatial niches were over-represented in high-bacterial burden granulomas. (12/20)

One of the most notable findings from this analysis is that T cell infiltration in the myeloid core VERY sharply drops off with the onset of hypoxia, something that is very evident in poor-controlling granulomas. (11/20)

With this approach we generated a consensus map of what we termed granuloma radial immunotopography. With this mapping we can model how cell phenotypes, metabolic niches, and functional programs coordinate with each other over 2D space. (10/20)

We next asked how hypoxia influences global granuloma structure and function? To do this, we teamed up with Russ Butler’s group at AdventHealth to adapt a radial topography algorithm from the geographical information system (GIS) field. (9/20)

P.S. Stay tuned for more to come re: microGIS

This gave us the chance to dig even deeper into the cellular phenotypes we identified in our imaging data. We confirmed the tight coupling of macrophage metabolism and functional state with increasing evidence that hypoxia is associated with suppressive and pathologic immune responses. (8/20)

AND my newly formed lab at the NIH (more on this later…) had also just done our first spatial transcriptomic pilot study on some of the same granulomas we evaluated with multiplexed imaging. (7/20)